CANCER-ASSOCIATED MUC1 MUCIN INHIBITS HUMAN T-CELL PROLIFERATION, WHICH IS REVERSIBLE BY IL-2

A number of adenocarcinomas abundantly express and secrete underglycos ylated MUC1 mucin. Underglycosylation exposes tandem repeat peptide se quences on cancer-associated MUC1 mucin that are normally cryptic. Hig h levels of MUC1 mucin are correlated with a poor prognosis and immuno suppression in adenocarcinoma patients. In this report we show that ca ncer-associated MUC1 mucin, affinity-purified from ascites fluids of c ancer patients, and synthetic tandem repeats of MUC1 mucin core peptid e can suppress human T-cell proliferative responses. This MUC1 mucin-i nduced suppression of T-cell responses can be reversed by the addition of exogenous IL-2 or anti-CD28 monoclonal antibody. These results are consistent with other studies showing that lymphocytes present in the vicinity of tumor cells are anergic and can be reactivated with exoge nous interleukin-2. Overcoming MUC1 mucin-induced immunosuppression wi th IL-2 combined with active specific immunotherapy might be an effect ive immunotherapeutic strategy against human adenocarcinomas.